We have refined the crystal structure of factor XIII zymogen using diffraction data collected at SSRL. There are two modes of activation: thrombin cleavage in the presence of low Ca2+, and high calcium concentration. We have subsequently determined the crystal structures of thrombin-cleaved factor XIII and of non-cleaved factor XIII in the presence of high concentrations of calcium and calcium analogues. In both these forms, the active site of the molecule remains obstructed. Continuing work is focused on the structural study of active factor XIII and its complexes with substrate analogues and inhibitors. Toward that end, we have grown weakly diffracting crystals of inhibited factor XIII.